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Title: De novo phasing with X-ray laser reveals mosquito larvicide BinAB structure [A potent binary mosquito larvicide revealed by de novo phasing with an X-ray free-electron laser]

Abstract

BinAB is a naturally occurring paracrystalline larvicide distributed worldwide to combat the devastating diseases borne by mosquitoes. These crystals are composed of homologous molecules, BinA and BinB, which play distinct roles in the multi-step intoxication process, transforming from harmless, robust crystals, to soluble protoxin heterodimers, to internalized mature toxin, and finally to toxic oligomeric pores. The small size of the crystals - 50 unit cells per edge, on average - has impeded structural characterization by conventional means. Here we report the structure of Lysinibacillus sphaericus BinAB solved de novo by serial-femtosecond crystallography at an X-ray free-electron laser. The structure reveals tyrosine- and carboxylate-mediated contacts acting as pH switches to release soluble protoxin in the alkaline larval midgut. An enormous heterodimeric interface appears to be responsible for anchoring BinA to receptor-bound BinB for co-internalization. Remarkably, this interface is largely composed of propeptides, suggesting that proteolytic maturation would trigger dissociation of the heterodimer and progression to pore formation.

Authors:
 [1];  [2];  [2];  [2];  [2];  [3];  [3];  [4];  [1];  [5];  [5];  [5];  [5];  [5];  [5];  [5];  [5];  [6];  [7];  [6] more »;  [7];  [4];  [3];  [2] « less
  1. Univ. Grenoble Alpes, CEA, CNRS, Grenoble (France)
  2. Univ. of California, Los Angeles, CA (United States)
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  4. Univ. of California, Riverside, CA (United States)
  5. SLAC National Accelerator Lab., Menlo Park, CA (United States)
  6. Univ. of California, Riverside, CA (United States); California Baptist Univ., Riverside, CA (United States)
  7. Stanford Univ., Stanford, CA (United States)
Publication Date:
Research Org.:
SLAC National Accelerator Lab., Menlo Park, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1350536
Alternate Identifier(s):
OSTI ID: 1378999
Grant/Contract Number:  
AC02-76SF00515; AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Nature (London)
Additional Journal Information:
Journal Name: Nature (London); Journal Volume: 539; Journal Issue: 7627; Journal ID: ISSN 0028-0836
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND TECHNOLOGY; 60 APPLIED LIFE SCIENCES; environmental biotechnology; protein delivery; nanocrystallography

Citation Formats

Colletier, Jacques -Philippe, Sawaya, Michael R., Gingery, Mari, Rodriguez, Jose A., Cascio, Duilio, Brewster, Aaron S., Michels-Clark, Tara, Hice, Robert H., Coquelle, Nicolas, Boutet, Sébastien, Williams, Garth J., Messerschmidt, Marc, DePonte, Daniel P., Sierra, Raymond G., Laksmono, Hartawan, Koglin, Jason E., Hunter, Mark S., Park, Hyun -Woo, Uervirojnangkoorn, Monarin, Bideshi, Dennis K., Brunger, Axel T., Federici, Brian A., Sauter, Nicholas K., and Eisenberg, David S. De novo phasing with X-ray laser reveals mosquito larvicide BinAB structure [A potent binary mosquito larvicide revealed by de novo phasing with an X-ray free-electron laser]. United States: N. p., 2016. Web. doi:10.1038/nature19825.
Colletier, Jacques -Philippe, Sawaya, Michael R., Gingery, Mari, Rodriguez, Jose A., Cascio, Duilio, Brewster, Aaron S., Michels-Clark, Tara, Hice, Robert H., Coquelle, Nicolas, Boutet, Sébastien, Williams, Garth J., Messerschmidt, Marc, DePonte, Daniel P., Sierra, Raymond G., Laksmono, Hartawan, Koglin, Jason E., Hunter, Mark S., Park, Hyun -Woo, Uervirojnangkoorn, Monarin, Bideshi, Dennis K., Brunger, Axel T., Federici, Brian A., Sauter, Nicholas K., & Eisenberg, David S. De novo phasing with X-ray laser reveals mosquito larvicide BinAB structure [A potent binary mosquito larvicide revealed by de novo phasing with an X-ray free-electron laser]. United States. doi:10.1038/nature19825.
Colletier, Jacques -Philippe, Sawaya, Michael R., Gingery, Mari, Rodriguez, Jose A., Cascio, Duilio, Brewster, Aaron S., Michels-Clark, Tara, Hice, Robert H., Coquelle, Nicolas, Boutet, Sébastien, Williams, Garth J., Messerschmidt, Marc, DePonte, Daniel P., Sierra, Raymond G., Laksmono, Hartawan, Koglin, Jason E., Hunter, Mark S., Park, Hyun -Woo, Uervirojnangkoorn, Monarin, Bideshi, Dennis K., Brunger, Axel T., Federici, Brian A., Sauter, Nicholas K., and Eisenberg, David S. Wed . "De novo phasing with X-ray laser reveals mosquito larvicide BinAB structure [A potent binary mosquito larvicide revealed by de novo phasing with an X-ray free-electron laser]". United States. doi:10.1038/nature19825. https://www.osti.gov/servlets/purl/1350536.
@article{osti_1350536,
title = {De novo phasing with X-ray laser reveals mosquito larvicide BinAB structure [A potent binary mosquito larvicide revealed by de novo phasing with an X-ray free-electron laser]},
author = {Colletier, Jacques -Philippe and Sawaya, Michael R. and Gingery, Mari and Rodriguez, Jose A. and Cascio, Duilio and Brewster, Aaron S. and Michels-Clark, Tara and Hice, Robert H. and Coquelle, Nicolas and Boutet, Sébastien and Williams, Garth J. and Messerschmidt, Marc and DePonte, Daniel P. and Sierra, Raymond G. and Laksmono, Hartawan and Koglin, Jason E. and Hunter, Mark S. and Park, Hyun -Woo and Uervirojnangkoorn, Monarin and Bideshi, Dennis K. and Brunger, Axel T. and Federici, Brian A. and Sauter, Nicholas K. and Eisenberg, David S.},
abstractNote = {BinAB is a naturally occurring paracrystalline larvicide distributed worldwide to combat the devastating diseases borne by mosquitoes. These crystals are composed of homologous molecules, BinA and BinB, which play distinct roles in the multi-step intoxication process, transforming from harmless, robust crystals, to soluble protoxin heterodimers, to internalized mature toxin, and finally to toxic oligomeric pores. The small size of the crystals - 50 unit cells per edge, on average - has impeded structural characterization by conventional means. Here we report the structure of Lysinibacillus sphaericus BinAB solved de novo by serial-femtosecond crystallography at an X-ray free-electron laser. The structure reveals tyrosine- and carboxylate-mediated contacts acting as pH switches to release soluble protoxin in the alkaline larval midgut. An enormous heterodimeric interface appears to be responsible for anchoring BinA to receptor-bound BinB for co-internalization. Remarkably, this interface is largely composed of propeptides, suggesting that proteolytic maturation would trigger dissociation of the heterodimer and progression to pore formation.},
doi = {10.1038/nature19825},
journal = {Nature (London)},
number = 7627,
volume = 539,
place = {United States},
year = {2016},
month = {9}
}

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